Sildenafil as citrate is FDA and EMEA approved for treatment of erectile dysfunction and pulmonary arterial hypertension (PAH).
There are also reports that sildenafil citrate is used for off-label indications including, but not limited to, prevention of high-altitude pulmonary edema associated with altitude sickness, treating lung fibrosis, primary pulmonary hypertension, secondary pulmonary hypertension, hypoxia induced pulmonary hypertension, neonatal pulmonary hypertension, pediatric pulmonary hypertension, nonoperable chronic thromboembolic pulmonary hypertension, severe coronary artery disease, age-related macular degeneration, brachial artery flow-mediated dilatation (in type 2 diabetes), Raynaud's syndrome, anal fissures, postmenopausal female sexual dysfunction, female sexual arousal disorder, digital ulcers secondary to systemic sclerosis, migraine, premature ejaculation, sickle-cell disease with pulmonary hypertension, achalasia (esophageal motility dysfunction), severe digital ischemia, recurrent ischemic priapism, severe lymphatic formation, congestive heart failure, diastolic dysfunction, tunical fibrosis, multiple sclerosis, intrauterine growth restriction, chronic pelvic pain, Alzheimer's disease, stroke, preeclampsia, gastroparesis, glucose dyscontrol in diabetes, primary dysmenorrheal pain, for increasing exercise capacity during hypoxia, increasing uterine artery blood flow and endometrial thickness to promote in-vitro fertilization (IVF).
Sildenafil citrate has also been proposed as a treatment for prostate cancer, pancreatic cancer, ovarian cancer, stomach cancer, obesity, Crohn's disease, spastic esophageal disorder, reduction of alcohol induced gastric damage and other conditions.
Sildenafil citrate is commonly marketed as VIAGRA® (for treatment of erectile dysfunction) and REVATIO® (for treatment of pulmonary hypertension), both manufactured by Pfizer Pharmaceuticals. Generic versions of sildenafil citrate are also available. VIAGRA® is commonly supplied as 25, 50 or 100 mg tablets and is to be taken not more than once per day 0.5 to 4 hours prior to intercourse. REVATIO® is most often supplied as 20 mg tablets to be taken 3 times daily. Sildenafil citrate are often labeled with the amount of sildenafil so that the actual amount of sildenafil citrate is about 30% more than the dosage/tablet indicated on the label.
REVATIO® is also available in injectable form as a clear colorless, sterile, ready to use solution containing 10 mg of sildenafil citrate per 12.5 ml of solution. Each ml of solution contains 1.124 mg sildenafil citrate, 50.5 mg dextrose and water for injection.
The injectable form of REVATIO® is most often administered intravenously. This route of administration is practical in a hospital setting but impractical outside a hospital or clinic setting.
In the EU sildenafil citrate is also available as an oral suspension at a concentration of 10 mg/ml. REVATIO® POS (powder for oral suspension) is supplied by Pfizer to be made up into an oral suspension. Additional ingredients in the POS include colloidal silicon dioxide, sucralose, sorbitol, sodium benzoate, sodium citrate, flavor and xanthan gum. The active ingredient in suspension has a slower absorption rate than would be expected for a solution with a similar concentration. In addition, the presence of some of the additional ingredients makes this product difficult to tolerate for people with known sensitivities to these ingredients.
Whether provided as tablets or oral suspension, sildenafil citrate exhibits an absolute bioavailability of about 41% and is reported to result in maximum observed plasma concentrations within 30 to 120 minutes following oral dosing in a fasted state. The rate of absorption is reportedly reduced if taken with a high fat meal.
According to the US package insert for VIAGRA®, solubility of sildenafil citrate in water is 3.5 mg/ml. The EMEA CHMP Assessment Report For Vizarsin (International Nonproprietary Name: sildenafil) indicates that it is insoluble in ethanol, chloroform and acetone but soluble in methanol and dimethylsulfoxide (DMSO). The Jordanian Pharmaceutical Manufacturing Co. reports that sildenafil citrate is about 3.5 times less soluble in ethanol than in water (˜1 mg/ml). The low water solubility of sildenafil citrate and/or its high presystemic elimination each independently contribute to its low oral bioavailability.